TY - JOUR
T1 - Kinase requirements in human cells
T2 - I. Comparing kinase requirements across various cell types
AU - Grueneberg, Dorre A.
AU - Degot, Sebastien
AU - Pearlberg, Joseph
AU - Li, Wenliang
AU - Davies, Joan E.
AU - Baldwin, Amy
AU - Endege, Wilson
AU - Doench, John
AU - Sawyer, Jacqueline
AU - Hu, Yanhui
AU - Boyce, Frederick
AU - Xian, Jun
AU - Munger, Karl
AU - Harlow, Ed
PY - 2008/10/28
Y1 - 2008/10/28
N2 - shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.
AB - shRNA loss-of-function screens were used to identify kinases that were rate-limiting for promoting cell proliferation and survival. Here, we study the differences in kinase requirements among various human cells, including freshly prepared primary cells, isogenic cells, immortalized cells, and cancer cell lines. Closely related patterns of kinase requirements among the various cell types were observed in three cases: (i) in repeat experiments using the same cells, (ii) with multiple populations of freshly prepared primary epithelial cells isolated from the same tissue source, and (iii) between nearly isogenic cells that differ from each other by the expression of a single gene. Other commonly used cancer cell lines were distinct from one another, even when they were isolated from similar tumor types. Even primary cells of different lineages isolated from the same tissue source showed many differences. The differences in kinase requirements among cell lines observed in this study suggest that the control of proliferation and survival may be significantly different between cell lines and that simple comparisons from any one cell to another may be misleading. Although the regulation of cell proliferation and survival are heavily studied areas, we did not see a bias in these screens toward the identification of previously known and well studied kinases, suggesting that our knowledge of molecular events in these areas is still meager.
KW - Cancer
KW - Essential kinases
KW - Fingerprints
KW - shRNA screens
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U2 - 10.1073/pnas.0808019105
DO - 10.1073/pnas.0808019105
M3 - Article
C2 - 18948591
AN - SCOPUS:55949117661
SN - 0027-8424
VL - 105
SP - 16472
EP - 16477
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 43
ER -